The convergence of nanotechnology and neuroscience holds promise for the successful development of external electronic devices capable of interfacing with the central nervous system (CNS). In recent years, considerable progress has been made in the fabrication of electronic devices at the micro- and nano-scales. However, it remains to be discovered how biological components can be successfully integrated with these devices. The long-term goal of our research project is to develop a series of hybrid neural prosthetic devices, consisting of biological components with digital integration that will allow the simultaneous measurement, and stimulation, of neural events in the CNS. The central hypothesis of this application is that the integration of biological components with neural prosthetic devices, will promote their successful integration with the mammalian CNS, to enhance long-term device performance. We will use research strategies from a variety of disciplines, including neuroscience, nanotechnology, computer sciences and engineering to accomplish our goals. The specific aims of this project are to: (i) develop methodologies for the design and construction of hybrid neural prosthetic devices; and, (ii) assess the functionality of hybrid devices in both in vitro and in vivo settings. The rationale for these studies is that, once we can reliably integrate biological components with neural prosthetic devices, that these basic design features will permit the construction of devices with additional biological units each of which possesses greater complexity. The research design is to use primary cultures of hippocampal pyramidal neurons as the biological components. Neurons will be incorporated with prosthetic devices, using a novel bio-mimetic polymer. The integration of hybrid devices into the CNS will be described using electrophysiological, pharmacological, and morphological methods. We envisage that end stage prosthetic devices will contain both organic and electrical components for providing inputs, controlling network function, and recording outputs. Presently 5.3 million Americans - approximately 2% of the U.S. population - live with disabilities resulting from a traumatic brain injury. The development of hybrid neural prosthetic devices will have the potential to restore function to people who suffer from a diverse range of neurological disabilities. [unreadable] [unreadable]